Protective Effect of FK506 on Myocardial Ischemia/Reperfusion Injury by Suppression of CaN and ASK1 Signaling Circuitry

被引：10

作者：

Feng, Xing ^{[2
]}

Li, Jing ^{[3
]}

Liu, Jinyu ^{[3
]}

Jin, Minghua ^{[2
]}

Liu, Xiaomei ^{[2
]}

Du, Haiying ^{[2
]}

Zhang, Long ^{[2
]}

Sun, Zhiwei ^{[1
,2
]}

Li, Xiaoguang ^{[1
]}

机构：

[1] Capital Univ Med Sci, Sch Publ Hlth & Family Med, Beijing 10054, Peoples R China

[2] Jilin Univ, Sch Publ Hlth, Changchun 130021, Jilin, Peoples R China

[3] Jilin Univ, Sch Basic Med, Changchun 130021, Jilin, Peoples R China

来源：

CARDIOVASCULAR TOXICOLOGY | 2011年 / 11卷 / 01期

基金：

英国科研创新办公室;

关键词：

Ischemia/reperfusion; CaN; Apoptosis; ASK1; FK506; CYCLOSPORINE-A;

D O I：

10.1007/s12012-010-9095-6

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

We investigated protective effect of FK506 on rat hearts subjected to ischemia/reperfusion (I/R) injury by regulating CaN and ASK1. Wistar rats were divided into four groups: Ischemia/reperfusion group (I/R), FK506 + Ischemia/reperfusion group (FK506-I/R), sham group, and FK506 + sham group (FK506-sham). Ischemia/reperfusion was achieved by occluding left coronary artery for 30 min and subsequently reperfusing for 120 min. FK506 was administered 15 min before ischemia. Rats in sham group and FK506-sham group were operated only by placing a ligature around the coronary artery, and the blood supply was not blocked. I/R group showed a rapid increase in TUNEL-positive cells and high risks of histopathological changes in damaged cardiac tissues. FK506 reduced the infarct size and inhibited the activation of CaN enzyme in FK506-I/R group. Increase in Bcl-2/Bax ratio in FK506-IR group indicated that FK506 protected myocardium from apoptosis induced by IR. The activity of CaN and ASK1 protein level decreased significantly after I/R injury in FK506-treated I/R heart. FK506 suppresses the activation of CaN and ASK1 through CaN-mediated apoptosis pathway, and ASK1 negatively regulates CaN activity. Suppression of CaN and ASK1 signaling circuitry are involved in protective effect of FK506 on rat myocardium I/R injury.

引用

页码：18 / 27

页数：10

共 40 条

[1]

Tacrolimus (FK506) versus cyclosporin a microemulsion (neoral) maintenance immunosuppression: effects on graft survival and function, infection, and metabolic profile following kidney transplantation (KT) [J].